POS0777 ADALIMUMAB AND ANTI-DRUG ANTIBODIES IN A COHORT OF CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS: A SINGLE-CENTER EXPERIENCE
Authors: G. Tarantino, D. Pires Marafon, F. Comitini, R. Simeoli, A. Aquilani, R. Nicolai, E. Marasco, F. De Benedetti, S. Magni-Manzoni
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Adalimumab (ADA), a fully humanized antibody against tumor necrosis factor (TNF)-α, has revolutionized treatment of patients with juvenile idiopathic arthritis (JIA). Although most of these respond within the first weeks, a minority may show loss of response (LOR) after continued exposure. Many studies demonstrate the influence of anti-adalimumab antibodies (AAA) on serum drug concentrations and clinical outcome in adults. However, little information about AAA and LOR is available for children with JIA. <h3>Objectives</h3> To describe demographic and clinical features in a single-center cohort of JIA patients treated with ADA, grouped according to frequency of drug administration (1W vs 2W); to assess ADA levels versus AAA titer and, finally, to investigate possible correlation between LOR to ADA and AAA. <h3>Methods</h3> Records of JIA patients on ADA treatment were retrospectively reviewed with focus on medical history and ELISA (enzyme-linked immunosorbent assay) ADA/AAA levels in a 12-month-period (Feb 2021-Feb 2022). Children with idiopathic uveitis were excluded. Samples furthest from last drug administration was defined as "trough level". Data were analyzed via descriptive statistics (STATA 15.1). <h3>Results</h3> Of 61 JIA patients treated with ADA (49% females), 38 had ANA positive oligoarthritis with almost one large joint involvement at disease onset (T0). None of them presented RF-positive polyarthritis, nor systemic JIA (s-JIA). The median age at T0 was about 3 years. Half of study cohort was b-DMARDS naive at ADA start (T1), while all children were on c-DMARDs. Chronic recurrent uveitis was the main reason for ADA starting, followed-by tenosynovitis and spine or hip active arthritis. At the first ADA/AAA sampling (T2), approximately 15% of patients had active disease, with elbows or wrists as the most frequently involved. Extreme variability was observed between AAA titers (median 7.4 AU/ml) and ADA levels (median 15.4 micrograms/ml), regardless from 1 or 2-weekly administration. ADA levels, compared to the days from last drug administration, reached plateau values corresponding to a pharmacokinetic steady state. Among both study groups, a possible inverse correlation between ADA and AAA was found. We identified 30 JIA patients with clinical (presence of arthritis or uveitis) or laboratory (ESR ≥15 mm/h; CRP&gt; 0.5 mg/dL) disease activity. Among these in only 6 we found very high AAA titers (350.0 - 113.4 AU/mL). In the subgroup of 37 patients with "trough-level" sampling heterogeneous data about AAA titers and drug level distribution were observed. <h3>Conclusion</h3> Our preliminary data showed a possible association between occurrence of AAA and lower ADA levels. However, a targeted risk analysis about high AAA titers and LOR incidence was not available. Monitoring of drug immunogenicity should be implemented in daily practice and become subject of future studies JIA. <h3>References</h3> [1]Brunelli et al. "Anti-adalimumab antibodies kinetics: an early guide for juvenile idiopathic arthritis (JIA) switvhing" Clin Rheumatol 2019 [2]Skrabl-Baumgartner A. et al. "Anti-adalimumab antibodies in juvenile idiopathic arthritis: frequent association with loss of response". Scand J Rheumatol 2015 [3]Imagawa T. et al. "Anti-adalimumab antibodies in a cohort of patients with juvenile idiopathic arthritis: incidence and clinical correlations". Clin Rheumatol 2018 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.